NOVEL ANCHORAGE OF GRUR2 3 TO THE POSTSYNAPTIC DENSITY BY THE AMPA RECEPTOR-BINDING PROTEIN ABP/

We report the cloning of alpha-amino-3-hydroxy-5-methyl-4-isoxazole pr opionic acid (AMPA) receptor-binding protein (ABP), a postsynaptic den sity (PSD) protein related to glutamate receptor-interacting protein ( GRIP) with two sets of three PDZ domains, which binds the GruR2/3 AMPA receptor subunits. ABP exhibits widespread CNS expression and is foun d at the postsynaptic membrane. We show that the protein interactions of the ABP/GRIP family differ from the PSD-95 family, which binds N-me thyl-D-aspartate (NMDA) receptors. ABP binds to the GruR2/3 C-terminal VKI-COOH motif via class II hydrophobic PDZ interactions, distinct fr om the class I PSD-95-NMDA receptor interaction. ABP and GRIP also for m homo- and heteromultimers through PDZ-PDZ interactions but do not bi nd PSD-95. We suggest that the ABP/GRIP and PSD-95 families form disti nct scaffolds that anchor, respectively, AMPA and NMDA receptors.